GPR40 is a seven transmembrane receptor that is expressed in a great number of tissues including the pancreatic islet cells, brain and gastrointestinal tract. The ligand stimulating this receptor is felt to be medium chain fatty acids. In 2005 we have succeeded in creating mice with homozygous deletion of the majority of the coding exon for the GPR40 gene and expressing the enhanced form of the green fluorescent protein as a fusion protein following the first 15 amino acids of GPR40. During the past year, we characterized the metabolic, biochemical and anatomic characteristics of GPR40 gene deleted mice compared to wild type littermates fed either a regular rat chow diet or a high fat diet. We also created three lines of transgenic mice expressing GPR40 under the control of the 5' upstream untranslated promoter region. Following the promoter region, the transgene consisted of the GPR40 cDNA fused at the carboxy-terminal tail with the enhanced green fluorescent protein cDNA. The entire transgenic construct was flanked by lox P sites. These mice will be used to determine GPR40 distribution and the metabolic effects of GPR40 overexpression. Using these GPR40 KO mice, we have shown that the mercaptoacetate induced feeding is mediated via the GPR40 fatty acid receptor.